Effects of mid-to-late prepartum feed supplementation in Hanwoo beef cows on their performance, blood metabolites, and the carcass characteristics and metabolites of their neonatal calves.

Introduction: This study aimed to evaluate the implications of supplementary nutrition during the mid-to-late pregnancy on various parameters in Hanwoo cows and their subsequent neonatal calves. Materials and methods: Eight Hanwoo cows in their first parity were divided into two groups. The control group (C, 100%) received 3kg of concentrate and 5kg of rice straw throughout the pregnancy period, while the treatment group (T, 150%) increased their diet during mid-to-late pregnancy. Both performance assessments and blood metabolite analyses were performed for the pregnant cows. Neonatal calves were subjected to morphometric evaluations, blood sampling, and detailed morphometric analyses of carcasses and gastrointestinal components. Results: Performance indices of the cows showed that both Pregnancy Period (PregP) and Body Condition Score (BCS) were significantly improved with supplemental feeding (p <0.05). Improvements in Body Weight (BW) and Feed Conversion Ratio (FCR) were not statistically significant. Blood metabolite analysis for the cows revealed decreased levels of triglycerides (TGLate), non-esterified fatty acids (NEFALate), and progesterone (P4Late), with a notable increase in glucose (GluLate) levels (p <0.01). In the neonatal calves, anatomical metrics of the gastrointestinal tissues showed increased Omasum Width (OmasWdth) values in the supplemented group (p =0.053). There was significant increase of papillae and villus lengths in the rumen and small intestine (p <0.01 and p <0.05, respectively). Morphometric evaluations displayed longer body lengths (BLnth) and larger chest width (ChestWdth) in the treated calves (p <0.05 and p <0.01, respectively). Carcass characteristics showed no substantial variations between the groups, while blood analysis in the calves revealed decreased GPT levels in the nutritionally supplemented group (p<0.05). Discussion: The findings indicate that supplementing the diets of Hanwoo cows during mid-to-late pregnancy leads to significant changes in select maternal blood metabolites and influences specific anatomical and morphometric features in neonatal calves, all without significant shifts in carcass attributes.

Genome-wide association study for carcass traits in Hanwoo cattle using additional relatives' information of non-genotyped animals.

The aim of this study was to find significant genomic regions associated with carcass traits in Hanwoo cattle and to compare the benefit of using additional information from non-genotyped animals. Imputed whole-genome sequence data were used along with phenotypic data on 13 715 genotyped animals as well as phenotypes of 440 284 non-genotyped animals that were offspring of 454 genotyped sires. For carcass weight, 15 083 SNPs in 33 QTL regions and 313 candidate genes were identified. We found 410 SNPs in 17 QTL regions containing 122 candidate genes for back fat thickness. In total, 656 SNPs in 19 QTLs with 137 candidate genes for eye muscle area and 79 SNPs in 12 QTL regions with 77 candidate genes were identified for marbling score. The most important candidate genes included ZFAT, TG, PLAG1, CHCHD7, and TOX for carcass weight and eye muscle area, NOG for back fat thickness, and EVOVL5 for marbling score. This study showed that the use of phenotypic records on non-genotyped progeny along with imputed whole-genome sequence data increased the power of detecting new significant genomic regions.

Oleic acid in Angus and Hanwoo (Korean native cattle) fat reduced the fatty acid synthase activity in rat adipose tissues.

This study aimed to determine the blood lipid profiles, fatty acid composition, and lipogenic enzyme activities in rat adipose tissues as affected by the Angus beef fat (ABF) and Hanwoo beef fat (HBF) containing high oleic acid (OA) content. We assigned 60 Sprague Dawley rats with a mean bodyweight of 249 ± 3.04 g to three groups (n = 20 each) to receive diets containing 7% coconut oil (CON), 7% ABF, or 7% HBF. The OA content was highest in the HBF (45.23%) followed by ABF (39.51%) and CON (6.10%). The final body weight of the HBF-fed group was significantly increased, probably due to increased feed intake, indicating the palatability of the diet. The HBF and ABF significantly increased high-density lipoprotein cholesterol (HDL-C), decreased triglyceride (TG) and total cholesterol (TC) levels, and also tended to attenuate glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels in the bloodstream of the rats compared to CON. As compared to CON, lauric, myristic, and palmitic acids were significantly lower, and those of OA and α-linolenic acid (ALA) were significantly higher in the adipose tissues of HBF and ABF-fed groups. The HBF and ABF also reduced lipogenesis as induced by depleted fatty acid synthase (FAS) activity in rat adipose tissues. Nevertheless, between the two fats, HBF showed high feed intake due to its high palatability but reduced lipogenic enzyme activity, specifically that of FAS, and increased HDL-C, decreased TC and TG levels in the bloodstream, reduced saturated fatty acids (SFA), and increased oleic and ALA contents in rat adipose tissues indicating that HBF consumption does not pose significant risks of cardiovascular disease.

High dietary oleic acid in olive oil-supplemented diet enhanced omega-3 fatty acid in blood plasma of rats.

This study was conducted to investigate the effect of dietary oleic acid in olive oil-supplemented diets on the blood lipid profile and fatty acid composition in blood plasma and adipose tissue of rats. A total of 60 Sprague Dawley rats with mean body weight of 249 g ± 3.04 g were equally divided into three diet groups: control (CON) contained 10% coconut oil, olive50 contained 5% coconut oil and 5% olive oil, and olive100 contained 10% olive oil. Oleic acid (OA) level was highest in olive100 followed by the olive50 and control. The final body weight (BW) of the rats was significantly affected by the intake of OA, in which rats fed olive100 had the lowest final BW, which signified that OA could be associated with weight loss. Olive oil intake significantly increased levels of the high-density lipoprotein cholesterol (HDL-C) and exhibited a potential attenuation effect on the glutamic-oxaloacetic transaminase and the glutamic-pyruvic transaminase, and a potential role in the reduction of triglycerides in the bloodstream of the animals. In terms of fatty acid composition, significantly high OA was observed in the blood plasma and adipose tissues of rats fed olive100. Omega-3 polyunsaturated fatty acids (PUFAs), such as linolenic (C18:3 n-3), eicosapentaenoic (C20:5 n-3), and docosahexaenoic (C22:6 n-3), and n-6 PUFA arachidonic (C20:4 n-6) were also significantly increased in the blood plasma of rats fed olive100. These findings suggest that the intake of dietary high OA may enhance the omega-3 fatty acid levels in the blood plasma of rats and may have a positive effect in reducing risks to cardiovascular disease, as evidenced by weight loss, increased HDL-C levels, and decreased TG levels in the blood plasma of experimental animals.

Citrus limonoid nomilin inhibits osteoclastogenesis in vitro by suppression of NFATc1 and MAPK signaling pathways.

BACKGROUND: Animal experiment studies have revealed a positive association between intake of citrus fruits and bone health. Nomilin, a limonoid present in citrus fruits, is reported to have many biological activities in mammalian systems, but the mechanism of nomilin on bone metabolism regulation is currently unclear. PURPOSE: To reveal the mechanism of nomilin on osteoclastic differentiation of mouse primary bone marrow-derived macrophages (BMMs) and the mouse RAW 264.7 macrophage cell line into osteoclasts. STUDY DESIGN: Controlled laboratory study. Effects of nomilin on osteoclastic differentiation were studied in in vitro cell cultures. METHODS: Cell viability of RAW 264.7 cells and BMMs was measured with the Cell Counting Kit. TRAP-positive multinucleated cells were counted as osteoclast cell numbers. The number and area of resorption pits were measured as bone-resorbing activity. Osteoclast-specific genes expression was evaluated by quantitative real-time PCR; and proteins expression was evaluated by western blot. RESULTS: Nomilin significantly decreased TRAP-positive multinucleated cell numbers compared with the control, and exhibited no cytotoxicity. Nomilin decreased bone resorption activity. Nomilin downregulated osteoclast-specific genes, NFATc1 and TRAP mRNA levels. Furthermore, nomilin suppressed MAPK signaling pathways. CONCLUSION: This study demonstrates clearly that nomilin has inhibitory effects on osteoclastic differentiation in vitro. These findings indicate that nomilin-containing herbal preparations have potential utility for the prevention of bone metabolic diseases.

Vagal hyperactivity due to ventromedial hypothalamic lesions increases adiponectin production and release.

In obese humans and animals, adiponectin production and release in adipose tissue are downregulated by feedback inhibition, resulting in decreased serum adiponectin. We investigated adiponectin production and release in ventromedial hypothalamic (VMH)-lesioned animals. VMH-lesioned mice showed significant increases in food intake and body weight gain, with hyperinsulinemia and hyperleptinemia at 1 and 4 weeks after VMH-lesioning. Serum adiponectin was elevated in VMH-lesioned mice at 1 and 4 weeks, despite adipocyte hypertrophy in subcutaneous and visceral adipose tissues and increased body fat. Adiponectin production and mRNA were also increased in both adipose tissues in VMH-lesioned mice at 1 week. These results were replicated in VMH-lesioned rats at 1 week. Daily atropine administration for 5 days or subdiaphragmatic vagotomy completely reversed the body weight gain and eliminated the increased adiponectin production and release in these rats, with reversal to a normal serum adiponectin level. Parasympathetic nerve activation by carbachol infusion for 5 days in rats increased serum adiponectin, with increased adiponectin production in visceral and subcutaneous adipose tissues without changes of body weight. These results demonstrate that activation of the parasympathetic nerve by VMH lesions stimulates production of adiponectin in visceral and subcutaneous adipose tissues and adiponectin release, resulting in elevated serum adiponectin.

Fish oil prevents excessive hepatic lipid accumulation without inducing oxidative stress.

We examined the effects of fish oil (FO) on high-cholesterol diet-induced hepatic lipid accumulation and oxidative stress. Female C57BL/6J mice were fed diets consisting of safflower oil (SO), 1 en% FO (1FO), 2 en% FO (2FO), or 20 en% FO (20FO) with or without 2 weight% (wt%) cholesterol (SO/CH, 1FO/CH, 2FO/CH, and 20FO/CH groups, respectively) for 8 weeks. The hepatic triacylglyceride levels were significantly lower in the 2FO/CH and 20FO/CH groups than in the SO/CH group. The hepatic mRNAs of fatty acid oxidation-related genes were upregulated and the fatty acid synthesis-related genes were downregulated by the FO feeding. Adverse effects were not observed in the plasma levels of indicators of oxidative stress in response to the consumption of FO up to 20 en%. These results suggest that FO consumption in the range of 2-20 en% prevents hepatic lipid accumulation, thus improving lipid metabolism without causing oxidative stress.

Effects of dietary fat energy restriction and fish oil feeding on hepatic metabolic abnormalities and insulin resistance in KK mice with high-fat diet-induced obesity.

We investigated the effects of dietary fat energy restriction and fish oil intake on glucose and lipid metabolism in female KK mice with high-fat (HF) diet-induced obesity. Mice were fed a lard/safflower oil (LSO50) diet consisting of 50 energy% (en%) lard/safflower oil as the fat source for 12 weeks. Then, the mice were fed various fat energy restriction (25 en% fat) diets - LSO, FO2.5, FO12.5 or FO25 - containing 0, 2.5, 12.5, or 25 en% fish oil, respectively, for 9 weeks. Conversion from a HF diet to each fat energy restriction diet significantly decreased final body weights and visceral and subcutaneous fat mass in all fat energy restriction groups, regardless of fish oil contents. Hepatic triglyceride and cholesterol levels markedly decreased in the FO12.5 and FO25 groups, but not in the LSO group. Although plasma insulin levels did not differ among groups, the blood glucose areas under the curve in the oral glucose tolerance test were significantly lower in the FO12.5 and FO25 groups. Real-time polymerase chain reaction analysis showed fatty acid synthase mRNA levels significantly decreased in the FO25 group, and stearoyl-CoA desaturase 1 mRNA levels markedly decreased in the FO12.5 and FO25 groups. These results demonstrate that body weight gains were suppressed by dietary fat energy restriction even in KK mice with HF diet-induced obesity. We also suggested that the combination of fat energy restriction and fish oil feeding decreased fat droplets and ameliorated hepatic hypertrophy and insulin resistance with suppression of de novo lipogenesis in these mice.

Low-dose fish oil consumption prevents hepatic lipid accumulation in high cholesterol diet fed mice.

We examined the effects of low-dose fish oil ingestion on hepatic lipid accumulation caused after high cholesterol feeding in C57BL/6J mice. The mice were fed purified experimental diets consisting of 20 energy % (en%) safflower oil (SO or SO/CH), 2 en% fish oil + 18 en% safflower oil (2FO or 2FO/CH), or 5 en% fish oil + 15 en% safflower oil (5FO or 5FO/CH) with or without 2 weight % (wt %) cholesterol for 8 weeks. Hepatic triglyceride and total cholesterol contents were significantly lower in groups that were fed diets containing fish oil and cholesterol than in those that were fed safflower oil and cholesterol. The hepatic mRNA levels of fatty acid synthase (FAS) were lower in groups fed cholesterol or fish oil. Fatty acid oxidation-related hepatic gene expressions were higher in fish oil-fed groups. Fecal cholesterol excretion was higher in all cholesterol-fed groups; cholesterol excretion was high in groups fed fish oil and cholesterol. These results suggest that low-dose fish oil diets improve lipid metabolism by modifying the expression of lipid metabolism-related genes in the liver and increasing fecal cholesterol excretion.

Effect of concomitantly used fish oil and cholesterol on lipid metabolism.

Although cholesterol plays various important roles in the body, when overconsumed, it causes atherosclerosis and results in ischemic heart disease. On the other hand, dietary fish oils contain n-3 fatty acids, such as eicosapentaenoic acid and docosahexaenoic acid, which prevent ischemic heart disease. This effect of n-3 fatty acids mainly results from the combined effects of inhibiting lipogenesis via a decrease of the mature form of sterol regulatory element-binding proteins (SREBPs) and stimulating fatty acid oxidation via peroxisome proliferator-activator receptor (PPAR) alpha activation in the liver. In this study, we examined the interactive effects on lipid metabolism of dietary 2% cholesterol (w/w) and 20% or 50% energy fish oil. In a safflower oil diet with 2% cholesterol, hepatic lipids accumulated. On the other hand, hepatic lipids did not accumulate in the fish oil diets with cholesterol. Furthermore, in the groups with fish oil energy ratios of 20%, the negative feedback control of cholesterol affected SREBP-2, and the actions of fish oil and cholesterol were equivalent, but this was not observed in the cases with fish oil energy ratios of 50%. The results of this study suggest that differences in lipid accumulation in the body are due to differences in lipid source and energy ratios which differentially impact the control of transcription factors by cholesterol.

Anti-obesity effect of fish oil and fish oil-fenofibrate combination in female KK mice.

AIM: The aim of our study is to elucidate the effects of EPA- or DHA-rich fish oil, and of the latter plus fenofibrate, on lipid metabolism in female KK mice. METHODS: Female KK mice were fed purified experimental diets containing lard/safflower oil (4:6, Lard/SO), EPA-rich fish oil (EPA), DHA-rich fish oil (DHA), or DHA-rich fish oil plus 0.2% (w/w) fenofibrate (DHA+FF) for 8 weeks. At the end of the experiments, we measured levels of plasma lipids, hepatic triglycerides, and cholesterol, as well as the hepatic mRNA expression of lipogenic and lipidolytic genes. RESULTS: The final body weight of EPA- and DHA-fed groups was significantly lower than that of the Lard/SO-fed group, and that of the DHA+FF-fed group was the lowest. All three fish oil treatments significantly reduced plasma insulin levels. Hepatic lipid levels significantly decreased in all three of these groups compared with the Lard/SO-fed group. Plasma adiponectin increased in both the EPA-and DHA-fed groups, but the increase was suppressed in the DHA+FF-fed group. Hepatocytes of Lard/SO-fed mice were filled with numerous fat droplets, but fat accumulation was inhibited in both EPA- and DHA-fed mice and was significantly prevented by fenofibrate treatment. SREBP-1c mRNA levels were decreased by about half in EPA- and DHA-fed mice compared with Lard/SO-fed mice. FAS, Insig-1, HMG-CoA reductase, and LDL-receptor mRNA levels also markedly decreased in both EPA- and DHA-fed mice, but there was no additional decrease in DHA+FF fed mice. Fenofibrate treatment significantly induced mRNA expression of AOX and UCP-2, but not of PPARalpha. CONCLUSION: These data suggest that fish oil inhibited body weight gain and exhibited an anti-obesity effect through the inhibition of lipid synthesis in female KK mice. Furthermore, fenofibrate treatment markedly inhibited body weight gain by the induction of fatty acid oxidation. Plasma adiponectin levels did not increase in mice fed DHA-rich fish oil with fenofibrate, although white adipose tissue (WAT) weight significantly decreased. We considered that adiponectin sensitivity increased more in mice fed DHA-rich fish oil with fenofibrate than in mice fed DHA-rich fish oil alone.

Interaction of fenofibrate and fish oil in relation to lipid metabolism in mice.

AIM: The aim of our study is to elucidate the interactive effects on lipid metabolism of fenofibrate and two fish oils with EPA and DHA contents in mice. METHODS: Female C57BL/6J mice were fed purified experimental diets containing safflower oil (SO), EPA-rich menhaden oil (MO) or DHA-rich tuna oil (TO) with or without 0.1% fenofibrate for 8 weeks. At the end of the experiments, we measured plasma lipids and hepatic triglycerides and cholesterol, and the hepatic mRNA expression of lipogenic and lipidolytic genes. RESULTS: Plasma TG levels fell in the group fed MO or TO alone and fell significantly in all fenofibrate-treated groups. Although plasma total cholesterol levels fell significantly in fish oil-fed groups, fenofibrate treatments increased significantly plasma total cholesterol levels in these fish oil groups, but not in the group fed SO alone; however, hepatic triglyceride and total cholesterol levels markedly decreased in MO-or TO-fed mice. In lipid synthesis, the hepatic mRNA level of SREBP-1c was not reduced in either fish oil group; however, Insig-1 mRNA decreased in MO and TO feeding groups by about half and FAS or SCD-1 mRNA decreased significantly in MO and TO feeding groups, compared with the SO feeding group. In both fish oil groups, SREBP-2 mRNA decreased significantly and HMG-CoA reductase mRNA also decreased with/without fenofibrate. On the other hand, fenofibrate supplementation significantly induced the mRNA expression of AOX and UCP-2, which play a role in lipid catabolism, in all diets. CYP7A1 mRNA increased markedly in mice fed MO diet with fenofibrate, compared with TO diet with fenofibrate. CONCLUSION: These data suggest that differences in dietary contents of EPA and DHA do not influence the inhibition of lipogenesis, and that fenofibrate supplementation stimulates fatty acid oxidation, regardless of the oil type; however, cholesterol catabolism was induced by a combination of EPA-rich fish oil and fenofibrate, which suggests that EPA has a greater synergistic ability for cholesterol catabolism induction by fenofibrate than DHA.

Stearoyl-CoA desaturase 1 gene expression is necessary for fructose-mediated induction of lipogenic gene expression by sterol regulatory element-binding protein-1c-dependent and -independent mechanisms.

Stearoyl-CoA desaturase (SCD) synthesizes oleate necessary for the biosynthesis of triglycerides and other lipids. Mice with a targeted disruption of the SCD1 gene are deficient in tissue oleate and have reduced expression of the sterol regulatory element-binding protein (SREBP) and its target genes. The SREBP-1c isoform is a known mediator of insulin action on hepatic gene expression, but its transcriptional effects due to glucose or fructose are still unclear. We found that fructose compared with glucose is a stronger inducer of SREBP-1c and lipogenic gene expression, causing a dramatic increase in hepatic triglyceride levels. However, when fed to the SCD1-/- mice, fructose failed to induce SREBP-1 or lipogenic genes and the triglyceride levels were not increased. Instead fructose feeding caused a decrease in hepatic glycogen and plasma glucose levels. The induction of SREBP-1 and lipogenic gene expression as well as the levels of liver triglycerides, glycogen, and plasma glucose was partially restored when the fructose diet was supplemented with very high levels of oleate (20% by weight) but not with palmitate, stearate, or linoleate. Fructose in a long term feeding induced the expression of SCD1 and that of other lipogenic genes in the liver of SREBP-1c-/- mice, and a further increase in expression of these genes occurred when the fructose diet was supplemented with oleate. Our observations demonstrated that oleate produced by SCD is necessary for fructose-mediated induction of lipogenic gene expression through SREBP-1c-dependent and -independent mechanisms and suggested that SCD1 gene expression is important in lipid and carbohydrate homeostasis.

A low fish oil inhibits SREBP-1 proteolytic cascade, while a high-fish-oil feeding decreases SREBP-1 mRNA in mice liver: relationship to anti-obesity.

Rodents fed fish oil showed less obesity with a reduction of triglyceride synthesis in liver, relative to other dietary oils, along with a decrease of mature form of sterol regulatory element binding protein-1 (SREBP-1) and activation of peroxisome proliferator-activated receptor alpha (PPARalpha). Decrease of mature SREBP-1 protein by fish oil feeding was due to either inhibition of SREBP-1 proteolytic cascade or to decrease of its mRNA. To clarify its mechanism and relation to antiobesity effect, mice were fed fish oil in a range from 10 to 60 energy percent (en%). Fish oil feeding decreased body weight and fat mass in a dose-dependent manner, in parallel with PPARalpha activation and a decrease of SREBP-1 mRNA. However, compared with 0 en% fish oil feeding, 10 en% fish oil feeding decreased mature SREBP-1 protein by 50% with concomitant decreases of lipogenic genes, while precursor SREBP-1 protein rather increased by 1.3-fold. These data suggest that physiological doses of fish oil feeding effectively decrease expression of liver lipogenic enzymes by inhibiting SREBP-1 proteolytic cascade, while substantial decrease of SREBP-1 expression is observed in its pharmacological doses, and that activation of PPARalpha rather than SREBP-1 decrease might be related to the antiobesity effect of fish oil feeding.

Dietary cholesterol opposes PUFA-mediated repression of the stearoyl-CoA desaturase-1 gene by SREBP-1 independent mechanism.

Stearoyl-CoA desaturase (SCD) catalyzes the rate-limiting step in the cellular synthesis of monounsaturated fatty acids, mainly oleate (18:1) and palmitoleate (16:1), which are the major monounsaturated fatty acids of membrane phospholipids, cholesteryl esters, waxes, and triglycerides. The mouse expresses three well-characterized SCD genes (SCD1, 2, and 3). SCD1 is the main isoform expressed in the liver of mice. Previous in vivo studies have shown that the transcriptional repression by n-3 and n-6 polyunsaturated fatty acids (PUFAs) and the induction by cholesterol of the SCD1 gene are dependent on the maturation of the sterol regulatory element-binding protein-1c (SREBP-1c). We studied the regulation of SREBP-1, SCD1, and other SREBP-1 target genes when a high cholesterol diet is combined with PUFA as n-6 PUFA rich soybean oil (SO), or n-3 PUFA rich fish oil (FO). While the PUFA/cholesterol (PUFA/CH) diets repressed the maturation of the SREBP-1, the SCD1 mRNA levels, and protein and enzyme activity were induced. Compared with PUFA diets, hepatic cholesterol ester and triglyceride were enriched with 16:1 and 18:1 monounsaturated fatty acids in mice fed PUFA/CH diets. Total plasma cholesterol levels were not altered but plasma triglycerides were reduced in SO/CH-fed mice compared with SO-fed mice. The mRNA for SREBP-1 was increased by the PUFA/CH diet but the mRNA levels of SREBP-1 target genes such as fatty acid synthase and LDL receptor were decreased, indicating that the main control of PUFA-mediated suppression of SREBP-1 target genes is the maturation of SREBP-1. This study demonstrates that cholesterol overrides the PUFA-mediated repression of the SCD1 gene and regulates SCD1 gene expression through a mechanism independent of SREBP-1 maturation.

Sterol regulatory element-binding proteins (SREBPs) as regulators of lipid metabolism: polyunsaturated fatty acids oppose cholesterol-mediated induction of SREBP-1 maturation.

Cellular cholesterol and fatty acid metabolism in mammals is controlled by a family of transcription factors called sterol regulatory element-binding protein isoforms, three of which (SREBP-1a, 1c, and 2) are well characterized. These proteins, which are synthesized as precursors, are inserted into the endoplasmic reticulum (ER) membrane with both the amino and carboxylic acid domains facing the cytosolic face of the membrane. In sterol-deficient cells, proteolytic cleavage of SREBPs occurs, thereby releasing their N-terminal mature and active forms and enabling them to enter the nucleus, where they bind to the sterol regulatory response element (SRE) and/or E-box sequences and activate genes involved in cholesterol, triglyceride, and fatty acid biosynthesis. Of the three SREBP isoforms, SREBP-1c gene expression is induced by cholesterol and repressed by polyunsaturated fatty acids (PUFA). We have examined the changes in SREBP-1c mRNA and protein levels as well as the mRNA levels of several SREBP-1c target genes when a high-cholesterol diet is combined with diets rich in PUFA of the n-6 series. Our studies show that PUFA oppose the cholesterol-mediated SREBP-1 maturation without affecting the cholesterol-mediated increase of SREBP-1c mRNA and precursor protein. The decrease in SREBP-1 mature protein paralleled the decrease in mRNAs for genes of fatty acid and cholesterol biosynthesis, such as HMG-CoA synthase and fatty acid synthase, but interestingly gene expression of stearoyl-CoA desaturase 1 (SCD1) was instead induced. These studies suggest that the main point of control of PUFA-mediated suppression of lipogenic gene expression is the inhibition of SREBP-1 maturation. The studies also reveal that the induction of SCD1 gene expression by cholesterol occurs through a mechanism independent of SREBP-1 maturation.